Draft Guidance

Section VI of this document addresses submission of GRAS notices. The GRAS notification procedure[2] is a voluntary procedure in which you inform us of your view that a particular use of a substance is exempt from the premarket approval requirements of the Act based on your determination that such use is GRAS in accordance with 21 CFR 170.30. We assign a file number (GRAS Notice No. (GRN)) to your submission and respond to you by letter.

A. General Information about Generally Recognized as Safe Notice Submissions

How do the parts on Form FDA 3667 relate to the elements of a GRAS notice?

Table VI-1 shows the elements of a GRAS notice and links each element to the applicable part of Form FDA 3667.

Table VI-1Elements of a GRAS Notice as Shown on Form FDA 3667

Element of a GRAS Notice

Applicable Part on Form FDA 3667

Introductory information about the submission

I

Information about the notifier (and any attorney or agent acting on behalf of the notifier)

II

General administrative information

III

Intended use

IV

Identity

V and VI

Method of manufacture

VI

Specifications

VI

Dietary exposure

VI

Self-limiting levels of use

VI

Common use in food before 1958 (if applicable)

VI

Comprehensive discussion of the basis for the GRAS determination

VI

Bibliography

VI

Signature

VII

N/A

VIII (List of Attachments)

How should I organize a new GRAS notice submission?

You should organize a new GRAS notice as a document presenting the elements of a GRAS notice in an order corresponding to that of the elements listed on Form FDA 3667. A summary of these elements is listed in Table VI-1 of this document and described in the instructions for Form FDA 3667 (see Appendix 5). If you include any data or information not identified on Form FDA 3667, you should place these data or information in a logical place in your submission based on the type of information.

You should organize an electronic GRAS notice submission using the foldering structure available in a downloadable GRAS Notice Submission Roadmap (see instructions in Appendix 5 and the roadmap in Appendix 15). The entire GRAS Notice Submission Roadmap is organized under the folder entitled “Main directory.” The “Main directory” includes three first-level folders, entitled “Administrative,” “GRAS Notice,” and “Incoming Correspondence.” The “Incoming Correspondence” folder includes three second-level subfolders entitled “Submission Form,” “Amendment” and “Supplement.” We show these folders and subfolders, using an outline format, in Figure VI-1, below.

Figure VI-1

Outline Representing the Folders and Subfolders in the “Main directory” of a GRAS Notice Submission Roadmap

·Main directory

Administrative

GRAS Notice

Incoming Correspondence

Submission Form

Amendment

Supplement

When should I use the specific folders and subfolders in the GRAS Notice Submission Roadmap?

You should use these folders and subfolders as shown in Table VI-2. You should not place any specific files directly in “Main directory.” “Main directory” only contains folders.

Table VI-2When to Use Specific Folders and Subfoldersin the “Main Directory” of a GRAS Notice Submission Roadmap*

Folder/Subfolder

When to Use it

Administrative

Any time you transmit a new GRAS notice or a redacted electronic file(s)

GRASNotice

Only when you transmit a new GRAS notice

IncomingCorrespondence

You should not place any specific files directly in the Incoming Correspondence folder. The Incoming Correspondence folder only contains subfolders.

Incoming Correspondence/Submission Form

Any time you transmit information while we are reviewing your GRAS notice or after we have responded to your GRAS notice

IncomingCorrespondence/ Amendment

Any time you transmit information while we are reviewing your GRAS notice

IncomingCorrespondence/ Supplement

Any time you transmit information after we have responded to your GRAS notice

* If you are transmitting an amendment or supplement to your GRAS notice, you should re-name “Main directory”to reflect the file number we assigned to your notice.

How should I name files in an electronic GRAS notice submission?

You should name each file using both generic and specific elements as described in Section III.C and Appendix 12 of this document. Generic elements in the file names specific to GRAS notice submissions are included in the examples in Table VI-3 (below).

What files should I place in each folder and subfolder?

Table VI-3Placement of Files in the GRAS Notice Submission Roadmap

Folder/Subfolder

File Name

Information in File

Administrative

Form3667_..._YYYY-MM-DD.pdf

Form FDA 3667 with responsive material completed

Administrative

CoverLetter_..._YYYY-MM-DD.pdf

Letter accompanying the submission if you choose to send a letter in addition to Form FDA 3667

Administrative

DesignationOfConfidential Information_..._YYYY-MM-DD.pdf

A description of the data or information in your submission that you designated as nondisclosable information (21CFR 20 Subpart D)

Administrative

RedactedBySubmitter_…_YYYY-MM-DD.pdf

Copy(ies) of one or more files in your submission modified by deletion of data or information you designated as nondisclosable information

GRASNotice

GRASNotice_..._YYYY-MM-DD.pdf

File containing the following information not placed on the form:

Table of Contents

Any additional information about identity not covered in Part IV of Form FDA 3667

Method of manufacture

Specifications for food-grade material

Dietary exposure

Self-limiting levels of use

Common use in food before 1958 (if applicable)

Comprehensive discussion of the basis for the determination of GRAS status

Bibliography

Other Information

GRASNotice

[Miscellaneous]_..._YYYY-MM-DD.pdf

One or more files containing miscellaneous information you ask FDA to consider in evaluating your GRAS notice (e.g., technical bulletins)

IncomingCorrespondence/ Submission Form

YYYY-MM-DD- Form3667_..._.pdf

Form FDA 3667 with responsive material completed

IncomingCorrespondence/ Amendment

YYYY-MM-DD_Amendment_....pdf

When applicable, file(s) containing the information you submit to us during our review of your GRAS notice. An amendment addressing more than one topic should include a Table of Contents.

IncomingCorrespondence/ Supplement

YYYY-MM-DD_Supplement_....pdf

When applicable, file containing the information you submit to us after we respond to your GRAS notice. A supplement addressing more than one topic should include a Table of Contents.

C. Electronic Amendments and Supplements to GRAS Notice Submissions

What recommendations apply to amendments and supplements to GRAS notice submissions?

You should refer to Section III.F of this document for general recommendations applying to amendments and supplements in electronic format.

When transmitting any amendment or supplement to a GRAS notice, you should organize your submission as a single file. If an amendment or supplement addresses more than one topic, the file should include a Table of Contents with bookmarks to aid in navigating through the submission. You then should place this file in the Incoming Correspondence/Amendment or Incoming Correspondence/Supplement subfolder in the GRAS Notice Submission.